Serum somatomedin-C Research Articles

Somatomedin-C and Procollagen Aminoterminal Peptide in Fibromyalgia

Objective: We wanted to examine serum Somatomedin-C [Sm-C] and procollagen aminoterminal peptide [PIIINP] in patients with fibromyalgia. Methods: Serum Sm-C level in 15 fibromyalgia patients was compared to levels from 15 controls, matched with respect to age and physical activity. Serum Sm-C and PIIINP were examined in 43 other patients to allow comparisons with reference values and correlations with clinical symptoms. Results: We found no difference in Sm-C levels among 15 patients compared to the control group. Similarity, the Sm-C values of 43 patients were not lower than the control group. Similarity, the Sm-C values of 43 patients were not lower than the control group, indeed 41 of the values were inside the 95% reference interval. Sm-C was significantly correlated to age but not to any of the clinical symptom scores. PIIINP was 12% lower [P < 0.01] than normal in the 43 fibromyalgia patients and its concentration correlated negatively to physical function measures. Conclusions: Abnormalities of neu...

Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

Somatomedin C (insulin‐like growth factor 1) in adults with Down's syndrome

In a Norwegian institution for the mentally retarded, 29 adults with chromosomally verified Down's syndrome were compared to other mentally retarded patients with respect to serum somatomedin C (SmC) (insulin-like growth factor 1 [IGF-1]). Contrary to what has been observed in children, no shortage of SmC could be demonstrated in the adults with Down's syndrome. The results were within the normal range, and there was no difference between those with Down's syndrome and the other mentally retarded patients. Human growth hormone (HGH) and body height were studied in a previous work. Some correlations with these data are, nevertheless, included herein because they are of relevance. SmC correlated with body height in Down's syndrome, while there was no correlation between SmC and HGH or between HGH and body height.

Abnormal growth hormone dynamics in chronic liver disease do not depend on severe parenchymal disease

Abnormal basal serum levels of growth hormone (GH) and abnormal GH dynamics have been observed in patients with alcoholic cirrhosis (AC). To further characterize these abnormalities, patients with AC or schistosomal hepatic fibrosis (SHF) were evaluated. The former patients have parenchymal liver disease, portal hypertension, and portosystemic shunting. SHF, in contrast, is characterized by periportal fibrosis with minimal or no parenchymal cell disease, portal hypertension, and portosystemic shunting. We studied 20 patients with SHF and normal stature and 15 patients with AC. In these two groups of patients, basal serum GH was higher than normal ( P < .01). A paradoxical increase in GH was observed during the oral glucose tolerance test (OGTT) in 55% of SHF and in 40% of AC patients. Significant GH elevation followed thyrotropin-releasing hormone (TRH) administration in 80% of SHF and 66% of AC patients, but not in normals. Serum nonsuppressible insulin-like activity (NSILA) and serum somatomedin C (Sm-C) levels were reduced significantly in both groups. In SHF patients, the paradoxical increase in GH during OGTT correlated inversely with Sm-C ( r = −.6, P < .05). We conclude that (1) abnormal GH secretion occurs in both SHF and AC, (2) serum Sm-C and NSILA are diminished in both forms of liver disease, and (3) portosystemic shunting of blood appears to be the important pathology shared by both forms of liver disease.

Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses

We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 +/- 15.4 pmol/l (+/- SD) in hyperthyroidism, 2.8 +/- 1.2 in hypothyroidism, 4.2 +/- 1.1 in NTI, and 5.3 +/- 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 +/- 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 +/- 3.2): these concentrations differed significantly from the mean control level (12.2 +/- 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r = 0.63; p less than 0.001, r = 0.65; p less than 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; p less than 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NTI.

Luteinizing hormone‐releasing hormone analogue (Buserelin) treatment for central precocious puberty: A multi‐centre trial

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Effects of chronic GRF treatment on lambs having low or normal birth weight

The effects of a long term treatment with human GRF(1–29)NH2 on plasma growth hormone (GH), somatomedin C (Sm-C), histomorphometric parameters of bone growth and body composition were investigated in normal and low birthweight male lambs. The animals were divided into two groups according to their birthweight: 24 normal birthweight (NBW) lambs weighing more than 4 kg and 22 low birthweight (LBW) lambs weighing less than 2.5 kg at birth. Half of the animals in each group received two daily subcutaneous injections (8 μg/kg body weight) of hGRF(1–29)NH2 (GRF) from birth to slaughter at 45 or 90 days of age. The other animals received the solvant only. At the beginning and at the end of the treatment, plasma GH and serum Sm-C concentrations were measured in all groups. After slaughter, a histomorphometric study was performed on undecalcified sections of metacarpal growth plates, and the remaining of the carcass was pulverized to study the chemical body composition. GRF induced GH release in both GRF-treated groups. However, plasma GH reached higher (P<.001) concentrations and the GRF-induced GH peak lasted longer in LBW than in NBW lambs. At day 45, the GRF treatment increased (P<.05) serum Sm-C concentrations in LBW. Most of histomorphometric parameters reflecting the metacarpal growth in length, were not statistically modified under GRF treatment. However, the size of degenerative cells was smaller (P<.05) in LBW treated lambs as compared to controls. Consequently, the cell production in the growth plate was increased (P<.05) under GRF treatment. In both NBW and LBW groups at 45 days of treatment, GRF treatment reduced the amounts of lipids (P<.025) and energy (P<.05), while increased (P<.01) phosphorus deposition in the body. In contrast, there was no effect of GRF treatment on protein content. We conclude from this experiment that the induction of GH secretion by a chronic treatment with GRF is able to modify some patterns of growth. However, most of the effects of GRF were observed in LBW lambs and after 45 days of treatment only. This suggests that treatment with GRF may serve to compensate for growth in growth-retarded animals. Further studies with different mode of GRF administration should indicate whether it is as much effective in normal animals.

Immunoreactive somatomedin C in children from Morocco: a biological marker of nutritional growth retardation ?

Somatomedin C (Sm-C) is supposed to be a sensitive marker of malnutrition. Its relationship to growth and protein intake was investigated in 47 Moroccan children. The children (mean age: 7.5 ± 2 yr) had no endocrine abnormality. Anthropometric parameters were measured, together with blood levels of Sm-C and growth hormone (GH). Lower values of Sm-C were found in the following situations: ( a) growth retardation ( more than −2 Sd, N = 23; Sm-C = 3.61 ± 0.42 nmol l vs. 13.38 ± 1.52, P < 0.02) ; ( b) body weight less than 80% of expected weight for height ( N = 8; Sm-C = 4.84 ± 0.97 vs. 10.33 ± 1.19, P < 0.02); ( c) boys with meat consumption less than 3 times per wk ( N = 15; Sm-C = 4.03 ± 0.71 vs. 12.35 ± 2.01, P < 0.002). Thus, lower values of Sm-C are found in association with weight insufficiency and lower protein intake. As has previously been assumed, serum Sm-C, which is regulated by nutrition, may be a sensitive tool in the assessment of nutritional status in developing countries such as Morocco. Furthermore, it could explain some cases of growth retardation in states of malnutrition.

Use of fibronectin and somatomedin-C as markers of enteral nutrition support in traumatized patients using a modified amino acid formula.

The purpose of this study was to evaluate the use of serum fibronectin and serum somatomedin-C as nutritional markers during enteral nutrition support (ENS) of critically ill, traumatized patients using an enteral product containing high concentrations of branched-chain amino acids. Twelve critically injured patients received a standard enteral formula with 30 g of a 44% branched-chain amino acid supplement added to each liter of formula. Fibronectin concentration, somatomedin-C concentration, and nitrogen balance were measured on study days 1, 4, 7, 14, 21, 28 or until adequate oral intake began. Both fibronectin and somatomedin-C concentrations increased significantly from baseline by day 7 of ENS. Nitrogen balance increased significantly from baseline by day 4. On days 14 and 21, only somatomedin-C and nitrogen balance increased significantly from baseline. Nitrogen balance was significantly correlated with somatomedin-C concentration (r = 0.53, p less than 0.01), cumulative caloric intake (r = 0.68, p less than 0.01), and cumulative nitrogen intake (r = 0.72, p less than 0.01). The results of this study suggest that serum somatomedin-C is useful and serum fibronectin has potential in monitoring nutrition support response in critically ill, traumatized patients.

96 DOSE-RESPONSE STUDIES WITH BIOSYNTHETIC HUMAN GROWTH HORMONE IN GROWTH HORMONE DEFICIENT PATIENTS

Increasing doses of biosynthetic human growth hormone (B-hGH) were given subcutaneously to 7 GH deficient subjects for three 14 days periods (2, 4 and 6 IU/day at 20.00 h) followed by 14 days without GH therapy. At the end of each period they were hospitalized for blood sampling. A dose-dependent increase in serum GH and somatomedin-C (Sm-C) levels occurred. However, the time course of the serum Sm-C patterns showed a significant fall in the evening during absence of therapy, a significant increase following infections of 2 IU of B-hGH, and constant levels within normal range during treatment with 4 and 6 IU. Plasma glucose was within normal range, with lower fasting levels (at 04.00 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a dose-dependent increase in the post-prandial insulin response. GH therapy increased serum levels of free fatty acids (p < 0.05) and 3-OH-butyrate but had no significant impact on serum triglyceride and cholesterol. We conclude that serum Sm-C levels show consistent GH dose-dependence, and that a GH replacement dose of 2 IU/day (1.5 IU/m2/day) is insufficient to maintain normal diurnal levels. Furthermore, a GH independent diurnal variation in these patients is suggested, and finally it is demonstrated that this authentic GH preparation possesses diabetogenic and lipolytic actions.

Long term pulsatile growth hormone (GH)-releasing hormone therapy in children with GH deficiency.

We treated seven GH-deficient children with 3-hourly 1 microgram/kg sc pulses of GHRH-(1-44) for 6 months and 2 micrograms/kg.pulse for another 6 months. Four patients had a serum GH response to iv GHRH before treatment, and an additional patient responded to iv GHRH after 1 month of pulsatile sc GHRH administration. The mean cumulative growth velocity increased from a pretreatment mean of 2.7 +/- 0.2 (+/- SE) to 8.4 +/- 2.5 and 5.4 +/- 0.7 cm/yr after 2 months and 1 yr of treatment, respectively. Low dose pulsatile GHRH therapy was effective in promoting growth in five of seven children, with height gain ranging from 4.4-7.5 cm at the end of 1 yr's therapy. Only one of the two patients who did not respond to GHRH had an improvement in linear growth when they were subsequently treated with synthetic GH. The other patient, a 16.5-yr-old pubertal girl who had both satisfactory GH and somatomedin-C responses during GHRH therapy, did not respond to either GHRH or, later, synthetic GH. The pretreatment serum GH response to iv GHRH, the serum somatomedin-C concentrations, and the peak serum GH response during sc GHRH therapy were not reliable predictors of clinical response.

Evaluation of hypothalamic dysfunction in growth hormone (GH)-deficient patients using single versus multiple doses of GH-releasing hormone (GHRH-44) and evidence for diurnal variation in somatotroph responsiveness to GHRH in GH-deficient patients.

To examine the efficacy of multiple doses of GHRH-44 to enhance GH secretion and to determine the number of GHRH-44 doses required to exclude hypothalamic dysfunction, 12 doses of GHRH-44 were administered iv every 2 h to 4 GH-deficient patients beginning in the morning (group A) and to 4 GH-deficient patients beginning in the evening (group B). Five additional GH-deficient patients (group C) were given 4-18 GHRH-44 doses. The first and last doses were 5 micrograms/kg; all others were 1 microgram/kg. Higher GH responses were attained by 9 of the 13 patients after multiple GHRH-44 doses than after the initial GHRH-44 dose. After the first GHRH-44 dose, the peak plasma GH concentrations were less than 7 micrograms/L in 9 patients; 4 of 9 achieved GH concentrations above 7 micrograms/L after 5-7 GHRH-44 doses; 2 had measurable levels below 7 micrograms/L. GH concentrations remained undetectable in 3 older patients in group C. In the patients who had detectable GH levels after GHRH-44 treatment, serum somatomedin-C concentrations increased from 0.67 +/- 0.14 (+/- SEM) to 0.79 +/- 0.14 U/mL after 6 GHRH-44 doses (P less than 0.01; n = 10) then to 1.00 +/- 0.14 (+/- SEM) U/mL after an additional 4-6 GHRH-44 doses (P less than 0.05; n = 9). After 6 GHRH-44 doses in groups A and B, the integrated GH concentrations between 2000 and 0800 h were greater than the integrated GH concentrations between 0800 and 2000 h (P less than 0.02). These findings indicate that a hypothalamic defect cannot be excluded on the basis of an impaired response to a single dose of GHRH-44, that the number of GHRH doses required to stimulate GH release in GH-deficient patients is variable, and that in addition to the possibility of genetically determined GHRH insensitivity some non-responding patients have developed severe acquired resistance to GHRH. Evidence for diurnal variation in the responsiveness of somatotropes to GHRH-44 in GH-deficient patients was also found.

GH binding to liver in young and old female rats: relation to somatomedin-C secretion.

Age-related changes in binding of 125I-bovine GH to liver membrane fractions were measured in female Long-Evans rats 2, 6, 12 and 20 months of age. Specific GH binding did not change between 2 and 6 months of age but increased significantly at 12 and 20 months of age. Scatchard analysis showed that the plots were curvilinear and consisted of high- and low-affinity binding sites. The age-related increases in binding sites were mainly due to an increase in number of low-affinity binding sites. Serum somatomedin-C (SM-C) levels in 20-month-old rats were about half those in the 6-month-old rats. Twice daily injections of ovine GH (2 mg/kg body wt) for 7 days depressed liver GH binding and increased serum SM-C levels in 19-month-old female rats, but had no effect on GH binding in 2-month-old female rats. These results suggest that the increase in liver GH binding sites and the decrease in SM-C secretion are associated with our previously reported decrease in GH secretion in old female rats.

Chemiluminescence immunoassay for somatomedin C in serum.

To select the best tracer for use in a competitive immunoassay, we conjugated human somatomedin C (SmC) to various chemiluminescent compounds via two different synthetic pathways. Naphthylhydrazides and arylhydrazides, used as the labels, were incorporated via their imidate or their succinimide esters. Conjugating the carboxy terminal of (amino ethyl)ethyl-isoluminol to SmC via a succinimide linkage supplied the most sensitive detection limit and the most immunoreactive conjugate. We developed an immunoassay based on the use of this conjugate, and evaluated dextran-coated charcoal, second-antibody precipitation, and solid-phase immunoprecipitation for separating bound and free label. This chemiluminescent method has a detection limit of 16 pg per tube, and it is accurate and precise. Correlation studies with a conventional radioimmunoassay (x) for SmC gave the following regression equation: y = 0.66x + 3.76 (r = 0.953, n = 30); the slight discrepancies between the two methods are probably ascribable to the use of different antibodies. We thus propose this chemiluminescence immunoassay as an inexpensive and sensitive alternative to radioimmunoassay for measuring SmC in serum or in extracts of serum.

SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years.

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.

Monoclonal and polyclonal antibodies compared for radioimmunoassay of somatomedin-C in patients with acromegaly or hypopituitarism.

We used a synthetic recombinant analog of somatomedin-C (Sm-C) to directly compare the performance of polyclonal and monoclonal antibodies for measuring Sm-C in serum of normal persons and in acromegalic or hypopituitary patients. Mean concentrations of Sm-C in healthy adults were 181 (SD 42) micrograms/L as measured with the monoclonal antibody, 194 (SD 61) micrograms/L with the polyclonal antibody. Both antisera gave excellent discrimination between acromegalics and normals. However, the assay with the polyclonal antibody was more sensitive than that with the monoclonal antibody (lower detection limits: 5 vs 100 micrograms/L) and thus better suited for quantifying Sm-C in samples from hypopituitary patients.

Serum Factor Responsible for Thymidine Uptake by Lymphocytes Is Independent of Somatomedin-C

ABSTRACT Lymphocytes have specific receptors for somatomedin-C (Sm-C) and GH. To test whether these cells are sensitive to the growth-promoting properties of these growth factors, we studied serum (with low or normal Sm-C and GH levels) from children having various statural disorders by means of the lymphocyte proliferation assay. Peripheral lymphocytes from each subject were cultured in media containing either autologous serum (AS) or normal pooled human serum (HS). The mitogenic response (MR) was assessed by determining the amount of tritiated thymidine incorporated into cellular DNA. The MR was studied both in phytohemagglutinin-stimulated and in unstimulated lymphocytes. MR was expressed as thymidine uptake (CPM) in the presence of AS divided by CPM in the presence of HS. The MR in serum from (1) 27 control subjects was 1.01 ± 0.03 (SEM); (2) 14 children with short stature and normal serum GH-RIA and Sm-C levels was 0.98 ± 0.04; and (3) 12 children with GH deficiency showed two widely different responses. In four patients (subgroup 1), the MR was 0.05 ± 0.02 and in eight (subgroup 2) the MR was 1.11 ± 0.06. Eleven patients were studied after GH therapy (three from subgroup 1), and the MR was 1.12 ± 0.03. Neither Sm-C levels nor linear growth rate correlated well with the growth-promoting property of the serum when tested on lymphocytes. In seven additional patients with GHD, the MR when studied at varying concentrations of serum (0.1–5.0%), showed results identical to subgroup 2. Addition of purified Sm-C to cultures did not enhance the MR of serum from GHD patients prior to GH therapy. GH-dependent factors other than Sm-C may have a role in in vitro lymphocyte proliferation; in its current form, however, this bioassay is not sensitive enough to be useful in the diagnosis of children with GH deficiency.

Growth hormone secretory patterns in children with short stature

To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.

Stimulation of in vitro muscle cell proliferation by sera from swine injected with porcine growth hormone.

The proliferation-promoting activity of sera obtained from pigs before and after porcine growth hormone injections was tested in a muscle cell culture bioassay. For 3 d, purified porcine growth hormone (pGH) was administered by intramuscular injection to crossbred barrows. Two levels of pGH were administered: 18 micrograms pGH X kg-1 body weight X d-1 (low dose) or 143 micrograms pGH X kg-1 body weight X d-1 (high dose). Multiple blood samples were withdrawn from jugular catheters for 3 d prior to the injection, during the injection period and for 6 d after the last injection. Although serum pGH levels in low-dose pigs were raised from two to three times pre-injection levels, there was no significant change in serum proliferation-promoting activity or somatomedin-C (SmC), insulin or cortisol levels during or after administration of pGH. In contrast, the proliferation-promoting activity of sera obtained during and after the high-dose pGH injections was higher (P less than .005) than the pre-injection levels. Serum pGH levels were increased approximately 30-fold by 4 h after each injection, and increases in SmC levels were observed 10 to 16 h after the pGH injection. During the injection period SmC levels increased from 1.7 to 4 times pre-injection levels. Insulin and cortisol levels did not change significantly during the 3-d treatment period. We believe that this muscle cell culture bioassay system will be a useful addition to traditional radioimmunoassays and whole animal studies in elucidating the mode of action of pGH in pituitary-intact swine.

Treatment of Silver-Russell type dwarfism with human growth hormone: Effects on serum somatomedin-C levels and on longitudinal growth studied by knemometry

Two patients, aged 5 and 12 years, with Silver-Russell type dwarfism are presented. As shown by standard tests and examination of the spontaneous nocturnal hGH secretion, there was only mild regulative hGH deficiency. HGH treatment was started with daily subcutaneous injections at age 5.5 years (height 90.3 cm, -6.1 SDS, bone age 2.75 years) and 12.6 years (height 125.7 cm, -3.7 SDS, bone age 8.75 years), respectively. Treatment was monitored by serial somatomedin-C (SM-C) determinations and by knemometry (lower leg measurement). SM-C values increased in both patients by 10.5 and 4.8 fold, respectively, and remained above the prepubertal range (greater than 2.5 U/ml) during the treatment periods of 1.5 years. Pretreatment knemometric growth rate was high (after a somatomedin generation test) in patient 1 (0.7 mm/week) and low in patient 2 (0.31 mm/week). It remained at the same level in patient 1 (0.67 mm/week) and increased markedly in patient 2 (0.46 mm/week). During a treatment interruption, in both patients, knemometric growth rates fell to 0.33 and 0.30 mm/week, respectively. After resumption of treatment, now with biosynthetic hGH, growth rates increased again in patients 1 and 2 to 0.64 and 0.48 mm/week, respectively. This lower leg growth pattern was parallelled by similar changes in total body growth velocity. Even after the relatively short treatment period of 14 to 16 months, a slight net gain in statural height could be observed, as standard deviation scores for bone age increased.